Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020.

BackgroundWomen are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown.AimWe assessed the impact of sex and gender on PASC in a Swiss population.MethodOur multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection.ResultsAmong those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41-1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03-1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74-1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01-1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03-1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29-2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60-0.97; p = 0.030).ConclusionSpecific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident.

Automated Quantitative Pupillometry in the Critically Ill: A Systematic Review of the Literature.

OBJECTIVE: A systematic literature search has been performed to identify potential confounders for outcome prediction using pupillary light reflex in adult critically ill patients, as measured by handheld automated pupillometry devices. METHODS: Three digital databases (PubMed, EmBase, Cochrane) were systematically searched. Articles published between 1990 and 2019 in adult patients using monocular automated handheld devices were considered. Studies were classified according to the Oxford Centre for Evidence-Based Medicine classification (level 1 represents the highest and level 5 the lowest level of evidence). Case reports, original research, and systematic reviews were included and cross-referenced. RESULTS: With the use of 202 search terms, 58 eligible articles reporting the use of handheld pupillometry in the critically ill could be identified, considering 3,246 patients. The highest level of evidence came from 10 randomized trials and 19 prospective observational studies. The level of evidence was mostly 2 to 3 and highest with studies regarding the potential confounding effects of pain, the use of opioids, and increased intracranial pressure. Additional potential confounders found are selective serotonin reuptake inhibitors, α2-adregenic receptor agonists, and NMDA antagonists. CONCLUSIONS: The pupillary light reflex is susceptible to factors resulting from underlying comorbid conditions and effects of treatment regimens. Scenarios frequently encountered in critical care such as pain, use of opioids, and proof of increased intracranial pressure have potential confounding effects on outcome and pupillary reflexes. When treatment is guided by pupillary metrics, such confounders put patients at risk of overtreatment or undertreatment. Future research should validate and identify additional confounders, because our review suggests that even more unexplored confounders may exist.

The Unease When Using Anesthetics for Treatment-Refractory Status Epilepticus: Still Far Too Many Questions.

Status epilepticus (SE), treatment-refractory status epilepticus (RSE), and super-treatment-refractory status epilepticus (SRSE) are associated with increased morbidity, mortality, and high socioeconomic burden and pose significant treatment challenges for intensivists and neurologists. To optimize and streamline emergency treatment, current practice guidelines recommend the use of continuously delivered intravenous anesthetic drugs such as midazolam, propofol, or barbiturates as the third-line therapy after first-line and second-line treatments have failed. Although the rationale for these third-line drugs seems intuitive at first glance, there is a clear paucity of evidence-based data on risks, benefits, and even on the choice of a third-line agent. Recent studies into safety and efficacy reveal disturbing results, such as a poor outcome and higher mortality associated with the use of intravenous anesthetic drugs, especially in patients with nonconvulsive SE without coma and in patients with out-of-hospital SE onset. Clinicians should deliberately weigh the advantages and disadvantages of intravenous anesthetic drug therapy in patients with different types of SE usually linked to a favorable outcome (i.e., simple partial, complex partial, or absence seizures). The lack of data to support evidence-based medicine prompts a careful balance of individual risks and benefits of intravenous anesthetic drug therapy in patients with SE, treatment-refractory SE, and super-RSE.

Emergency management of status epilepticus in a high-fidelity simulation: A prospective study.

OBJECTIVES: To quantify the quality of physicians' emergency first response to status epilepticus (SE) and to identify risk factors for nonadherence to treatment guidelines in a standardized simulated scenario. METHODS: In this prospective trial, 58 physicians (of different background) of the University Hospital Basel, a Swiss academic medical care center, were confronted with a simulated SE. Primary outcomes were time to (1) airway protection, (2) supplementary oxygen, and (3) administration of antiseizure drugs (ASDs). RESULTS: All physicians recognized ongoing seizures. Airways were checked by 54% and protected by 16% within a median of 3.9 minutes. Supplementary oxygen was administered by 76% with a median of 2.8 minutes. First-line ASDs were administered by 98% (benzodiazepines 97% within a median of 2.9 minutes), and second-line ASDs by 57% within 8.1 minutes. Regarding secondary outcomes, the median time to monitor blood pressure and heart rate was 1.8 (interquartile range [IQR] 1.3-2.6) and 2.0 (IQR 1.4-2.7) minutes, respectively. Neurologic affiliation of physicians was associated with inadequate assessments of vital signs (odds ratio [OR] = 0.2; 95% CI 0.04-0.93) and most frequent administration of second-line ASDs (OR = 5.0; 95% CI 1.01-25.3). Knowing treatment guidelines and subjective certainty regarding SE diagnosis were associated with frequent administration of second-line ASDs (OR = 10.4; 95% CI 1.2-88.1). CONCLUSIONS: Nonadherence to SE treatment guidelines is frequent. The lack of airway assessment and protection in the simulated clinical scenario of SE may increase mortality and promote treatment refractoriness related to aspiration pneumonia. Guideline-based clinical training is urgently needed to increase the quality of SE management. REGISTRATION: ISRCTN registry (ID ISRCTN60369617; www.isrctn.com/ISRCTN60369617).

Untangling operational failures of the Status Epilepticus Severity Score (STESS).

OBJECTIVE: To uncover clinical characteristics leading to false outcome prediction of the Status Epilepticus Severity Score (STESS), a validated and broadly used clinical scoring system for outcome prediction in status epilepticus (SE). METHODS: From 2005 to 2016, adult patients with SE treated at the University Hospital Basel, Switzerland, were included. To assess independent associations of variables differing between patients with false and correct prediction of death (STESS ≥ 3), multivariable logistic regression models were computed using automated selection. RESULTS: Among 467 patients, 12% died. The median STESS was 3 (interquartile range 2-4). Regarding prediction of death, the STESS was false-positive in 51% and false-negative in 1%. Patients surviving despite having a STESS ≥3 had less fatal etiologies, less nonconvulsive SE with coma, and lower Charlson Comorbidity Index, Simplified Acute Physiology Score II, and Acute Physiology and Chronic Health Evaluation II scores. In multivariable analyses, odds for survival were high with SE types other than nonconvulsive status with coma and low with an increasing Charlson Comorbidity Index in patients with a STESS ≥ 3 (odds ratio [OR]for survival 4.23, 95% confidence interval [CI] 2.33-9.60; and ORfor survival 0.86, 95% CI 0.75-0.98). In patients with SE types other than nonconvulsive with coma, the STESS was mainly increased because they were frequently older than 65 years and had no seizure history. CONCLUSIONS: The STESS frequently and inadequately predicts death especially in patients with SE other than nonconvulsive with coma and few comorbidities. Clinicians are urged to interpret a STESS ≥3 with caution in such patients.

Prolonged status epilepticus: Early recognition and prediction of full recovery in a 12-year cohort.

OBJECTIVES: Early identification of patients who are at risk of prolonged status epilepticus (SE) and patients with high chances of full recovery despite prolonged SE may urge clinicians to intensify treatment rather than to withdraw care. We aimed to develop prediction models based on readily available clinical parameters to predict prolonged SE at seizure onset and to identify patients with high chances for full recovery. METHODS: From 2005 to 2016, all adult SE patients treated at the University Hospital Basel, a Swiss medical care center, were included. Multivariable Poisson regression was performed to identify predictors of prolonged SE (defined as SE for >12, >24, and >48 hours) and return to baseline from prolonged SE. The area under the receiver-operating characteristic curves (AUROC) for prediction models was calculated. RESULTS: Of 467 patients, the median age was 66.7 years and mortality was 12%. Relative risk (RR) for death was 1.06 (P < 0.0001) with every SE day. In multivariable analysis, nonconvulsive SE with coma, SE severity score ≥3, and acute brain lesions at SE onset independently predicted prolonged SE with an AUROC of 0.68 for >12, 0.67 for >24, and 0.72 for >48 hours of SE. Absence of nonconvulsive SE with coma and a decreasing Charlson comorbidity index were independent predictors for return to baseline in prolonged SE with an AUROC of 0.82 and 0.76 following cross-validation. Both associations remained significant despite adjustments for determinants of adverse outcome, such as anesthetics and vasopressors (nonconvulsive SE with coma RR = 0.24, 95% confidence interval [CI] 0.07-0.86; comorbidity index RR = 0.87, 95% CI 0.76-0.99). SIGNIFICANCE: Although our data indicate that identification of prolonged SE at seizure onset is unreliable, timely recognition of patients with high chances of good outcome despite prolonged SE is promising on the basis of comorbidities, type of SE, and level of consciousness. Further external validation of this prediction model is needed.

The unnatural history of pulmonary stenosis up to 40†years after surgical repair.

OBJECTIVE: To provide prospective information on long-term outcome after surgical correction of valvular pulmonary stenosis (PS). METHODS: Fifty-three consecutive patients operated for PS during childhood between 1968 and 1980 in one centre are followed longitudinally for 37±3.4 years, including extensive in-hospital examination every 10 years. RESULTS: Survival information was available in 100% of the original 53 patients. Cumulative survival was 94% at 20 years and 91% at 40 years. Excluding perioperative mortality (<30 days), survival was 94% at 40 years. Of 46 eligible survivors, 29 participated in the in-hospital examination and 15 gave permission to use their hospital records (96% participation). Cumulative event-free survival was 68% after 40 years: 25% needed a reintervention, 12% underwent pacemaker implantation and 9% had supraventricular arrhythmias. Early reinterventions were mainly for residual PS, late reinterventions for pulmonary regurgitation. Subjective health status was good. Exercise capacity was normal in 74% (median 96 (82-107)% of expected workload). Right ventricular and left ventricular (LV) dysfunction was found in 13% and 41%, respectively. The use of a transannular patch and younger age at surgery were predictive for late events (HR 3.02 (95% CI 1.09 to 8.37) and HR 0.81/year (95% CI 0.66 to 0.98), respectively). Use of inflow occlusion compared with cardiopulmonary bypass showed a trend towards more reinterventions (HR 3.19 (95% CI 0.97 to 10.47)). CONCLUSIONS: Survival up to 40 years after successful PS repair is nearly normal. Subjective health status is good and there is a low incidence of arrhythmias. Reinterventions, however, are necessary in one-quarter and 40 years postoperatively several patients show LV dysfunction.

Pregnancy mitigates cardiac pathology in a mouse model of left ventricular pressure overload.

In Western countries heart disease is the leading cause of maternal death during pregnancy. The effect of pregnancy on the heart is difficult to study in patients with preexisting heart disease. Since experimental studies are scarce, we investigated the effect of pressure overload, produced by transverse aortic constriction (TAC) in mice, on the ability to conceive, pregnancy outcome, and maternal cardiac structure and function. Four weeks of TAC produced left ventricular (LV) hypertrophy and dysfunction with marked interstitial fibrosis, decreased capillary density, and induced pathological cardiac gene expression. Pregnancy increased relative LV and right ventricular weight without affecting the deterioration of LV function following TAC. Surprisingly, the TAC-induced increase in relative heart and lung weight was mitigated by pregnancy, which was accompanied by a trend towards normalization of capillary density and natriuretic peptide type A expression. Additionally, the combination of pregnancy and TAC increased the cardiac phosphorylation of c-Jun, and STAT1, but reduced phosphoinositide 3-kinase phosphorylation. Finally, TAC did not significantly affect conception rate, pregnancy duration, uterus size, litter size, and pup weight. In conclusion, we found that, rather than exacerbating the changes associated with cardiac pressure overload, pregnancy actually attenuated pathological LV remodeling and mitigated pulmonary congestion, and pathological gene expression produced by TAC, suggesting a positive effect of pregnancy on the pressure-overloaded heart.

Longitudinal development of psychopathology and subjective health status in CHD adults: a 30- to 43-year follow-up in a unique cohort.

OBJECTIVE: To determine longitudinal changes in psychopathology in a cohort of patients 30-43 years after their first cardiac surgery for Congenital Heart Disease (CHD) in childhood, to compare outcomes of the 30- to 43-year follow-up with normative data, and to identify medical predictors for psychopathology. METHODS: This study is the third follow-up of this cohort. The first and second follow-ups of this same cohort were conducted in 1990 and 2001, respectively. At all three follow-ups, psychopathology was assessed with standardised, parallel questionnaires. In 2011, subjective health status was assessed by the Short Form-36. Medical predictor variables were derived from medical examinations and medical records. RESULTS: In this third follow-up, a total of 252 patients participated. Of these, 152 patients participated in all three follow-ups. Over a 30-year period, proportions of patients showing psychopathology decreased significantly. At the 30- to 43-year follow-up, overall outcomes on psychopathology for the CHD sample were similar or even better compared with normative groups. Subjective health status was also better compared with normative data. No differences were found between cardiac diagnostic groups. Medical variables that predicted the course of psychopathology over time were as follows: the scar, as judged by the patient, results of the first cardiac surgery, and the number of hospitalisations. CONCLUSIONS: Over a 30-year period, psychopathology decreased in patients with CHD. Levels of psychopathology in these patients, who are now aged between 30 and 54 years, were comparable or even better than normative data.

The unnatural history of the ventricular septal defect: outcome up to 40 years after surgical closure.

BACKGROUND: Few prospective data are available regarding long-term outcomes after surgical closure of a ventricular septal defect (VSD). OBJECTIVES: The objective of this study was to investigate clinical outcomes>30 years after surgical VSD closure. METHODS: Patients who underwent surgical VSD closure during childhood between 1968 and 1980 were reexamined every 10 years. In 2012, we invited eligible patients to undergo another examination, which included electrocardiography, Holter monitoring, echocardiography, bicycle ergometry, measurement of N-terminal pro-B-type natriuretic peptide, and subjective health assessment. RESULTS: Cumulative survival was 86% at 40 years. Causes of mortality were arrhythmia, heart failure, endocarditis, during valvular surgery, pulmonary hypertension, noncardiac causes, and unknown causes. Cumulative event-free survival after surgery was 72% at 40 years. Symptomatic arrhythmias occurred in 13% of patients and surgical or catheter-based reinterventions in 12%. Prevalence of impaired right ventricular systolic function increased from 1% in 2001 to 17% in 2012 (p=0.001). Left ventricular systolic function was impaired but stable in 21% of patients. Aortic regurgitation occurred more often in the last 20 years (p=0.039), and mean exercise capacity decreased (p=0.003). N-terminal pro-B-type natriuretic peptide (median: 11.6 pmol/l [interquartile range: 7.0 to 19.8 pmol/l]) was elevated (>14 pmol/l) in 38% of patients. A concomitant cardiac lesion, for example, patent ductus arteriosus, and aortic cross-clamp time were determinants of late events (hazard ratio: 2.84 [95% confidence interval: 1.23 to 6.53] and hazard ratio: 1.47 per 10 min [95% confidence interval: 1.22 to 1.99], respectively). Patients rated their subjective health status significantly better than a reference population. CONCLUSIONS: Survival up to 40 years after successful surgical VSD closure is slightly lower than in the general Dutch population. Morbidity is not negligible, especially in patients with a concomitant cardiac lesion.

Sports participation in adults with congenital heart disease.

BACKGROUND: It is unclear whether sports participation in adults with repaired congenital heart disease is safe and has benefits. METHODS: Congenital heart disease (ConHD) patients who underwent corrective surgery for Atrial Septal Defect, Ventricular Septal Defect, Pulmonary Stenosis, Tetralogy of Fallot or Transposition of the Great Arteries in our center between 1968 and 1980 were included, and participated in our longitudinal follow-up study with serial evaluations in 2001 and 2011. At both time points patients filled in questionnaires on sports participation, subjective physical functioning and quality of life. Exercise testing, echocardiogram and 24-hour continuous ambulatory ECG-monitoring were performed in both 2001 and 2011. All clinical events (re-intervention, arrhythmia, heart failure) were prospectively recorded. RESULTS: No relationship was found between practicing sports and the occurrence of sudden death, PVCs or SVTs. Patients with moderate/complex forms of ConHD practiced fewer hours of sports compared with the general Dutch normative population. Patients with both simple and moderate/complex ConHD who practiced sports showed a higher exercise capacity. More favorable subjective physical functioning was found for moderate/complex patients who practiced sports. CONCLUSIONS: Adults with repaired ConHD are less often involved in sports than the Dutch general population. The patients that were engaged in sports show a higher exercise capacity than those who did not. Sports participation in patients with ConHD was not associated with an increased incidence of adverse cardiac events.

Association between N-terminal pro-brain natriuretic peptide and quality of life in adult patients with congenital heart disease.

AIMS: Advances in medical treatment have resulted in increased life expectancy in congenital heart disease. Consequently, the focus of management has shifted from reducing mortality to reducing long-term morbidity with the goal of improving quality of life. A predictor of quality of life might be N-terminal pro-brain natriuretic peptide, a well-established marker for heart failure. We aimed to determine the association between N-terminal pro-brain natriuretic peptide and quality of life in patients with congenital heart disease. METHODS: We collected blood samples from consecutive patients who were initially operated between 1968 and 1980 (47.8% women; mean age 40.2±5.4 years). The 36-item Short-Form Health Survey was completed to assess subjective health status as a measure of quality of life. Analysis was performed for the entire group and for subgroups defined as simple versus complex congenital heart diseases. Median N-terminal pro-brain natriuretic peptide level was 15.2 pmol/L (overall range 1.3-299.3 pmol/L). N-terminal pro-brain natriuretic peptide levels were associated with the subdomain physical functioning (ß=-0.074, p=0.031). This association remained significant after adjustment for age and sex (ß=-0.071, p=0.038) and after adjustment for age, sex, body mass index, left ventricular function, and renal function (ß=-0.069, p=0.048). In complex congenital heart disease, the association between N-terminal pro-brain natriuretic peptide and physical functioning remained significant in multivariable analysis (ß=-0.076, p=0.046). No associations were found in the simple congenital heart disease group or on the other health status subdomains. CONCLUSION: In adults operated for congenital heart disease, N-terminal pro-brain natriuretic peptide is associated with the subdomain physical, primarily in the complex subgroup.

Psychosocial functioning of adults with congenital heart disease: outcomes of a 30-43 year longitudinal follow-up.

OBJECTIVE: Investigating long-term psychosocial and emotional outcomes, 30-43 years after cardiothoracic surgery during childhood. METHODS: Adult patients (N = 252, aged 33-55 years) all operated between 1968 and 1980 for atrial septal defect, ventricular septal defect, pulmonary stenosis, tetralogy of Fallot or transposition of the great arteries (TGA, all Mustard) were evaluated in the Erasmus MC. Psychosocial and emotional functioning were measured using standardized, validated questionnaires. Results in 2011 were compared with those found in 2001. RESULTS: Compared with normative data, the total sample showed significant impairments on living conditions, relationships, occupational level and income, but a better quality of life and emotional functioning. Patients with moderate/complex ConHD reported significantly more physical restrictions and felt more often at a disadvantage because of their ConHD compared with those with simple ConHD. From 2001 to 2011, outcomes on biographical characteristics (living conditions, marital status and income) improved significantly, though still impairments were found. CONCLUSION: At 30-43 year follow-up, compared to normative data, patients had a better quality of life and emotional functioning, despite impairments on occupational level and income. Compared to patients with simple defects, patients with moderate/complex ConHD scored worse on multiple outcomes, which warrants special attention for these patients.

Unnatural history of tetralogy of Fallot: prospective follow-up of 40 years after surgical correction.

BACKGROUND: Prospective data on long-term survival and clinical outcome beyond 30 years after surgical correction of tetralogy of Fallot are nonexistent. METHODS AND RESULTS: This longitudinal cohort study consists of the 144 patients with tetralogy of Fallot who underwent surgical repair at <15 years of age between 1968 and 1980 in our center. They are investigated every 10 years. Cumulative survival (data available for 136 patients) was 72% after 40 years. Late mortality was due to heart failure and ventricular fibrillation. Seventy-two of 80 eligible survivors (90%) participated in the third in-hospital investigation, consisting of ECG, Holter, echocardiography, cardiopulmonary exercise testing, N-terminal pro-brain natriuretic peptide measurement, cardiac magnetic resonance (including dobutamine stress testing), and the Short Form-36 questionnaire. Median follow-up was 36 years (range, 31-43 years). Cumulative event-free survival was 25% after 40 years. Subjective health status was comparable to that in the normal Dutch population. Although systolic right and left ventricular function declined, peak exercise capacity remained stable. There was no progression of aortic root dilation. A previous shunt operation, low temperature during surgery, and early postoperative arrhythmias were found to predict late mortality (hazard ratio, 2.9, 1.1, and 2.5, respectively). An increase in QRS duration and a deterioration of exercise tolerance and ventricular dysfunction did not predict mortality. Insertion of a transannular patch was a predictor for late arrhythmias (hazard ratio, 4.0; 95% confidence interval, 1.2-13.4). CONCLUSIONS: Although many patients needed a reoperation or developed arrhythmias, late mortality was low, and the clinical condition and subjective health status of most patients remained good. Previous shunt, low temperature during surgery, and early postoperative arrhythmias were found to predict late mortality.

The natural and unnatural history of the Mustard procedure: long-term outcome up to 40 years.

AIMS: To describe long-term survival, clinical outcome and ventricular systolic function in a longitudinally followed cohort of patients after Mustard repair for transposition of the great arteries (TGA). There is serious concern about the long-term outcome after Mustard repair. METHODS AND RESULTS: This longitudinal single-centre study consisted of 91 consecutive patients, who underwent Mustard repair before 1980, at age <15 years, and were evaluated in-hospital every 10 years. Survival status was obtained of 86 patients. Median follow-up was 35 (IQR 34-38) years. Cumulative survival was 84% after 10 years, 80% after 20 years, 77% after 30 years, and 68% after 39 years. Cumulative survival free of events (i.e. heart transplantation, arrhythmias, reintervention, and heart failure) was 19% after 39 years. Reinterventions were mainly required for baffle-related problems. Supraventricular and ventricular arrhythmias occurred in 28 and 6% of the patients, respectively. Pacemaker and/or ICD implantation was performed in 39%. Fifty survivors participated in the current in-hospital investigation including electrocardiography, 2D-echocardiography, cardiopulmonary-exercise testing, NT-proBNP measurement, Holter monitoring, and cardiac magnetic resonance. Right ventricular systolic function was impaired in all but one patient at last follow-up, and 14% developed heart failure in the last decade. NT-proBNP levels [median 31.6 (IQR 22.3-53.2) pmol/L] were elevated in 92% of the patients. Early postoperative arrhythmias were a predictor for late arrhythmias [HR 3.8 (95% CI 1.5-9.5)], and development of heart failure [HR 8.1 (95% CI 2.2-30.7)]. Also older age at operation was a predictor for heart failure [HR 1.26 (95% CI 1.0-1.6)]. CONCLUSION: Long-term survival after Mustard repair is clearly diminished and morbidity is substantial. Early postoperative arrhythmias are a predictor for heart failure and late arrhythmias.

Long-term psychosocial outcome of adults with tetralogy of Fallot and transposition of the great arteries: a historical comparison.

OBJECTIVE: To make a historical comparison on the long-term psychosocial outcome of cardiothoracic surgery during childhood. METHODS: Adult patients operated for tetralogy of Fallot or transposition of the great arteries between 1980 and 1990 (recent sample) were compared with patients who underwent surgery and were investigated 10 years earlier (historical sample). In addition, atrial switch and arterial switch patients within the recent sample were compared. Psychosocial functioning was measured using standardised, validated psychological questionnaires. RESULTS: Although the recent sample of patients overall shows a favourable quality of life, impairments were found in income, living conditions, relationships, offspring, and occupational level. Compared with the historical sample, the recent sample showed no significant improvements on psychosocial functioning, except for a better educational level. The amount of educational problems, such as learning difficulties, was still high compared with normative data. Recently operated patients with transposition of the great arteries (arterial switch) scored significantly better on the Short Form-36 vitality scale (p = 0.02) compared with historical patients with transposition of the great arteries (atrial switch). CONCLUSIONS: Despite improvements in medical treatment over the past few decades, hardly any change was found in the psychosocial outcome of the recent patient sample compared with the historical patient sample. In particular, the percentage of patients needing special education and showing learning problems remained high, whereas income was low compared with normative data.

N-terminal pro-B-type natriuretic peptide and its relationship with cardiac function in adults with congenital heart disease.

OBJECTIVES: The aim of this study was to determine the value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in adults with congenital heart disease (CHD) and investigate its relationship with ventricular function and exercise capacity. BACKGROUND: NT-proBNP may detect early deterioration in cardiac function. METHODS: In this cross-sectional study, extensive echocardiography, exercise testing, and NT-proBNP measurements were performed on the same day in consecutive adult patients with CHD. RESULTS: In total, 475 patients were included in this study (mean age of 34 ± 12 years, 57% male, 90% New York Heart Association class I). The median NT-proBNP level was 15.1 pmol/l (interquartile range [IQR]: 7.1 to 31.3 pmol/l), and the NT-proBNP level was >14 pmol/l in 53% of patients. The highest NT-proBNP levels were observed in patients with Fontan circulation (36.1 pmol/l [IQR: 14.4 to 103.8 pmol/l]) and a systemic right ventricle (RV) (31.1 pmol/l [IQR: 21.8 to 56.0 pmol/l]), and the lowest values were seen in patients with aortic coarctation (7.3 pmol/l [IQR: 2.8 to 19.5 pmol/l]). NT-proBNP levels correlated with age (r = 0.39, p < 0.001) and were higher in women (median of 21.7 vs. 10.4 pmol/l; p < 0.001). In patients with aortic stenosis or aortic coarctation, NT-proBNP levels correlated with diastolic function parameters of E/E' ratio (r = 0.40, p < 0.001) and left atrial dimension (r = 0.36, p < 0.001). In patients with a systemic RV, NT-proBNP levels correlated with RV annulus diameter (r = 0.31, p = 0.024). In patients with tetralogy of Fallot, the strongest correlations were observed with left atrial dimension (r = 0.46, p < 0.001) and left ventricular ejection fraction (r = 0.37, p < 0.001). NT-proBNP levels were associated with exercise capacity (n = 198) (maximum workload: ß = -0.08, p = 0.021) and peak oxygen uptake (ß = -0.012, p = 0.011) in a multivariable regression model adjusted for age and sex. CONCLUSIONS: NT-proBNP levels in adults with CHD clearly differ by diagnosis and are related to echocardiographic parameters and exercise capacity. Disease-specific correlations contribute to the understanding of the main hemodynamic problems per diagnosis. Follow-up data are needed to elucidate the additional prognostic value.